The development strategy for an effective tetravalent dengue vaccine has consisted of the clinical evaluation of monovalent vaccine candidates for each of the four serotypes with the goal of selecting suitable candidates for inclusion in a tetravalent formulation. Previously, monovalent vaccine candidates were evaluated in a combined total of over 500 human subjects to determine safety, infectivity, and immunogenicity. These studies identified a collection of 6 suitable vaccine candidates: DEN1del30, DEN2/4del30, DEN3del30/31, DEN3-3D4del30, DEN4del30, and DEN4del30-200,201. The selected vaccine candidates were safe and asymptomatic, elicited a robust antibody response in more than 80% of subjects, and were highly infectious (50% infection dose < 10 PFU). Tetravalent studies: Previously, several Phase I clinical studies were completed to evaluate five different tetravalent admixtures of each vaccine candidate. From this set of data, an optimal admixture (TV-003: DEN1del30, DEN2/4del30, DEN3del30/31, DEN4del30) was selected and induces an unprecedented level of neutralizing antibody that is both balanced among the serotypes and sufficient to provide sterile immunity against a second dose administered at six months. These data suggest that a single dose of vaccine may be sufficiently immunogenic, which points to a significant advantage of the LID vaccine compared to other live attenuated DENV vaccines which require two or three doses to achieve a similar result. The selection of an optimal tetravalent admixture has enabled the further development of the vaccine by several manufacturers located in Brazil, India, and Vietnam. Through on-going technological and scientific support, these licensees are making significant progress in the development of the vaccine and some will soon enter Phase 2 trials in their own countries. At LID, clinical evaluation of TV-003 in an expanded number of both naive subjects (NCT01436422) and flavivirus sero-positive subjects (NCT01506570) is currently underway. Should future studies of this vaccine prove it to be efficacious, the vaccine could be a cost-effective means of controlling dengue in endemic areas and a tremendous public health asset.